Meropenem trihydrate (meropenem.3H2O) [Chemical name: (4R,5S,6S)-3-((3S,5S)-5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-6-((R)-1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, trihydrate] is a compound having the structure of the following formula (1):

As a prior art regarding a synthesis of meropenem, U.S. Pat. No. 4,943,569 discloses a method for obtaining amorphous meropenem by coupling-reacting MAP with a side chain material as shown in Reaction Scheme 1 below to prepare meropenem-PNB whose carboxylic group is protected by p-methoxybenzyl group or p-nitrobenzyl group, dissolving it in an appropriate amount of a mixture solvent of tetrahydrofuran and ethanol, hydrogenating at room temperature for 3 hours in a buffer solution of morpholinopropanesulfonic acid in the presence of 10% palladium-carbon with 120% of weight ratio, filtering the catalyst, evaporating tetrahydrofuran and ethanol under vacuum, washing the residual solution with ethyl acetate, evaporating the solvent in an aqueous solution under vacuum, isolating by column chromatography using CHP-20P, and freeze-drying.

In addition, U.S. Pat. No. 4,888,344 introduces a method for obtaining meropenem trihydrate by dissolving meropenem-PNB in a mixture solvent of tetrahydrofuran (THF) and water, adding 10% palladium-carbon thereto and reacting it under hydrogen atmosphere (4.8 atm) at room temperature for 5 hours, filtering the catalyst, evaporating tetrahydrofuran under vacuum, washing the residual solution with dichloromethane, evaporating the solvent in an aqueous solution under vacuum, concentrating by using reverse osmosis condensing apparatus and crystallizing. As compared with the method of U.S. Pat. No. 4,943,569, since the method of U.S. Pat. No. 4,888,344 does not use a morpholinopropanesulfonic acid buffer solution and conducts the catalyzed hydrogenation reaction in a mixture solvent of water and tetrahydrofuran, it is advantageous that the hydrate can be obtained directly from the aqueous concentrated liquid without using the procedures of column chromatography, freeze-drying, isolation and recovery.
Furthermore, Korean Laid-open Patent Publication No. 1994-14399 improves the yield of the final target compound by introducing a novel process for synthesizing meropenem-PNB which can reduce the production procedures and carry out the production easily, as compared with a conventional method. However, since this method also employs the deprotection procedure of meropenem-PNB of U.S. Pat. No. 4,943,569, a crystallization procedure is further conducted after obtaining meropenem in an amorphous form to obtain more stable trihydrate, resulting in meropenem trihydrate yield of 55.3% (deprotection reaction yield: 69.1%; crystallization yield: 80%).
The above methods have complex processes and use very expensive devices. In particular, they require the expensive palladium-carbon in a large amount. Furthermore, since highly explosive hydrogen gas should be used, they are difficult to industrialize.